Search results for "Phenotype"

2015

Characterization of host-pathogen interactions is a fundamental approach in microbiological and immunological oriented disciplines. It is commonly accepted that host cells start to change their phenotype after engulfing pathogens. Techniques such as real time PCR or ELISA were used to characterize the genes encoding proteins that are associated either with pathogen elimination or immune escape mechanisms. Most of such studies were performed in vitro using primary host cells or cell lines. Consequently, the data generated with such approaches reflect the global RNA expression or protein amount recovered from all cells in culture. This is justified when all host cells harbor an equal amount o…

Genetic dissection of plexin signaling in vivo

2014

Mammalian plexins constitute a family of transmembrane receptors for semaphorins and represent critical regulators of various processes during development of the nervous, cardiovascular, skeletal, and renal system. In vitro studies have shown that plexins exert their effects via an intracellular R-Ras/M-Ras GTPase-activating protein (GAP) domain or by activation of RhoA through interaction with Rho guanine nucleotide exchange factor proteins. However, which of these signaling pathways are relevant for plexin functions in vivo is largely unknown. Using an allelic series of transgenic mice, we show that the GAP domain of plexins constitutes their key signaling module during development. Mice …

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

2020

Abstract Background Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. Methods We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results wer…

Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related d…

2022

Abstract Background Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. Methods This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000–2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing–remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers’ characteristics, geographic macro-ar…

FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis.

2013

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy with a strong epigenetic component. It is associated with deletion of a macrosatellite repeat leading to over-expression of the nearby genes. Among them, we focused on FSHD region gene 1 (FRG1) since its over-expression in mice, Xenopus laevis and Caenorhabditis elegans, leads to muscular dystrophy-like defects, suggesting that FRG1 plays a relevant role in muscle biology. Here we show that, when over-expressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. Moreov…

P.20.3 Targeting fibrosis and inflammation in Duchenne Muscular Dystrophy

2013

Duchenne Muscular Dystrophy is the most frequent genetic muscle disease worldwide affecting ∼1:5000 male births. It is caused by a defective DMD gene, which leads to reduced and defective dystrophin protein expression. The constant breakdown of fibres leads to focal necrosis, myophagocytosis and a considerable influx of inflammatory cells into the muscle tissue, which is followed by increasing endomysial fibrosis. Both, inflammation and fibrosis as well as a putative relation are not yet understood immunologically. Fibrosis directly correlates with adverse outcome and early loss of ambulation. We have studied how inflammation is linked to fibrosis in DMD, with an emphasis on the communicati…

Lactobacillus uvarum sp. nov. - A new lactic acid bacterium isolated from Spanish Bobal grape must

2008

Five strains isolated from grape musts in Spain in 1997, have been characterized by several molecular techniques, and three of them have been identified as pertaining to a new species. All strains are Gram-positive rods, aerotolerant and homofermentative bacteria that do not exhibit catalase activity. Phylogenetic analysis based on 16S rRNA gene sequences placed these strains within the genus Lactobacillus, closely related to Lactobacillus mali. DNA-DNA hybridization experiments confirmed that strain 71 belongs to the lately described species L. satsumensis, strain 88 belongs to L. mali and the other three isolates have an independent status at species level. Restriction analysis of the amp…

The Candida albicans pH-regulated KER1 gene encodes a lysine/glutamic-acid-rich plasma-membrane protein that is involved in cell aggregation.

2004

Immunoscreening of aCandida albicanscDNA library with a polyclonal germ-tube-specific antibody (pAb anti-gt) resulted in the isolation of a gene encoding a lysine/glutamic-acid-rich protein, which was consequently designatedKER1. The nucleotide and deduced amino acid sequences of this gene displayed no significant homology with any other known sequence.KER1encodes a 134 kDa lysine (14·5 %)/glutamic acid (16·7 %) protein (Ker1p) that contains two potential transmembrane segments.KER1was expressed in a pH-conditional manner, with maximal expression at alkaline pH and lower expression at pH 4·0, and was regulated byRIM101. A Δker1/Δker1null mutant grew normally but was hyperflocculant under ge…

The effect of genetic robustness on evolvability in digital organisms

2008

Abstract Background Recent work has revealed that many biological systems keep functioning in the face of mutations and therefore can be considered genetically robust. However, several issues related to robustness remain poorly understood, such as its implications for evolvability (the ability to produce adaptive evolutionary innovations). Results Here, we use the Avida digital evolution platform to explore the effects of genetic robustness on evolvability. First, we obtained digital organisms with varying levels of robustness by evolving them under combinations of mutation rates and population sizes previously shown to select for different levels of robustness. Then, we assessed the abilit…

A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy

2020

Diseases associated with acquired or genetic defects in members of the chaperoning system (CS) are increasingly found and have been collectively termed chaperonopathies. Illustrative instances of genetic chaperonopathies involve the genes for chaperonins of Groups I (e.g., Heat shock protein 60, Hsp60) and II (e.g., Chaperonin Containing T-Complex polypeptide 1, CCT). Examples of the former are hypomyelinating leukodystrophy 4 (HLD4 or MitCHAP60) and hereditary spastic paraplegia (SPG13). A distal sensory mutilating neuropathy has been linked to a mutation [p.(His147Arg)] in subunit 5 of the CCT5 gene. Here, we describe a new possibly pathogenic variant [p.(Leu224Val)] of the same subunit b…